SYNERGISM OF ITRACONAZOLE AND CYCLOPHOSPHAMIDE NANOPARTICLES FOR BREAST CANCER; SYNTHESIS, CHARACTERIZATION AND CYTOTOXICITY

Abstract

Itraconazole has been known and used as anti-fungal drug for many years. But recently, clinical evidence has demonstrated the potential anticancer activity of itraconazole. Cyclophosphamide on the other hand, is a medication that particularly has been utilized in the management and treatment of several types of cancer since decades. In order to enhance the cancer immunotherapy response, the synthesis of nanoparticles has been suggested to be an effective way for smart targeted delivery of drug and to enhance the pharmacokinetic parameters of the drugs. Recently, Chitosan has been studied extensively due to its novel property of drug carrying capacity. This pertains to various advantages such as biodegradability, good biocompatibility and non-toxic properties. The purpose of this study is to evaluate the synergistic anti-cancer effects of chitosan loaded nanoparticles of itraconazole and cyclophosphamide on the breast cancer cells i.e.MCF-7. The ionic gelation method was used to produce Chitosan loaded nanoparticles of both Cyclophosphamide and Itraconazole. For the characterization of nanoparticles, the particle size analysis, FTIR and SEM were used. Furthermore, drug loading, entrapment efficiency and in-vitro dissolution profiles were evaluated.

The mean or average diameter of chitosan and Chitosan based Cyclophosphamide nanoparticles were in range 335.9nm and 213nm respectively, while 412nm for chitosan based Itraconazole nanoparticles. The deviation in the size of particles described that by addition of drug in affected their particle sizes. Average of the particle size for Chitosan NPs was slightly bigger than the CYP-CS-NPs whereas smaller than that of ITR-CS-NPs. Also, the efficiency regarding encapsulation of CYP-CS-NPs and ITR-CS-NPs was 62.4% and 98.79%, respectively (as per method). This is due to because the high polymer: drug ratio used that allowed the more drugs can be encapsulated inside core. The SEM analysis revealed that surface of drug-free chitosan nanoparticles; Cyclophosphamide-loaded chitosan nanoparticles and Itraconazole loaded nanoparticles were spherical along with some bands. Kinetic parameters like release profiles (in-vitro), regarding CYP-CS-NPs and ITR-CS-NPs showed good sustained-release up to 50% at 8hours. ITR showed sustaining properties due to its bigger size and better encapsulation efficiency. The cytotoxic-studies established that ITR-CS-NPs possess anti-cancer activity the against MCF7 cell-lines and can be repurposed for it’s used along with cyclophosphamide for the effective treatment of Breast Cancer.